Study Design and Population

To study the effect of donor category (deceased vs. living, ECDs vs. SCDs), we carried out a retrospective, single-center, observational, cohort analysis of patients with borderline changes early after transplantation. Of 6,197 kidney recipients transplanted at our center between January 2005 and January 2017, all borderline changes were retrospectively identified (12.6%). Only patients with BL from case biopsies performed early after transplantation [median 9 days (min 4, max 60)] were enrolled in our study cohort (n = 338) (Figure 1). To obtain a cohort of borderline changes as a first pathology, all cases with prior episodes of rejection or thrombotic microangiopathy were excluded. To determine pure BL pathology, cases with concurrent presence of antibody-mediated rejection (ABMR), thrombotic microangiopathy (TMA), recurrent glomerulonephritis, glomerulitis >1, and BK virus (BKV) nephropathy were excluded. Furthermore, patients with primary graft dysfunction were deemed ineligible to participate in the study. A final cohort of 269 patients with early BL biopsies as a first and sole pathology was formed, with midterm outcomes compared between ECD (n = 109), SCD (n = 109), and LD (n = 51) categories. Expanded criteria donor kidneys were obtained from deceased donors either aged ≥ 60 years or 50–59 years meeting at least two of the following conditions: serum creatinine >1.5 mg/dL (132.5 μmol/L), cerebrovascular accident as a cause of death, or history of hypertension (9). Standard criteria donors are all deceased donors who failed to meet the criteria for ECD (10). Living donor kidney transplantation was performed between ABO-compatible genetically related or unrelated relatives or friends or with non-directed donors when kidney paired donation was performed. All kidney transplant recipients were treated according to standard center protocol, receiving no induction, T cell–non-depletive (basiliximab, daclizumab) induction, or T cell–depletive induction (rATG or infliximab) followed by a standard triple immunosuppression regimen based on a combination of tacrolimus/cyclosporine, mycophenolate mofetil (MMF)/mycophenolic acid (MPA), and steroids.

Flowchart of the study.

For the purpose of the transcriptomic study, we analyzed only patients receiving no induction or non-depletive induction therapy to eliminate the effect of different posttransplant immunosuppression on expression profiles. Furthermore, only biopsies performed within the first 14 days after transplantation were analyzed to reduce time-dependent changes in transcriptional profiles. Thus, the final cohort for molecular analysis consisted of 21 patients across 3 donor categories: ECD, SCD, and LD. Demographics of the microarray cohort are given in Table 1.

Demographics of patient groups analyzed by microarray.

The study was approved by ethics committee of the Institute for Clinical and Experimental Medicine and Thomayer Hospital With Multi-center Competence under number G-16-06-09.